The overall objectives of this research proposal to be accomplished through the use of immuno-electron microscopy are three-fold: a) to establish the localization and distribution of the surface antigen(s) of primate sporozoites by using hybridoma-derived antibodies, b) to determine the intracellular distribution of the percursor in the different developmental stages of plasmodia, and c) to characterize at the ultrastructural level the in vitro interaction of sporozoites with a hepatoma cell line (HepG2-a16), with regard to sporozoite adherence, penetration and intracellular development in the presence of either non-specific immunoglobulin, normal serum or monoclonal antibodies. Determination of the intracellular distribution of the precursors of protective sporozoite antigens will be studied by ultra-thin frozen sections and/or freeze fracture techniques followed by immuno-cytochemical electron microscopy. This study will clarify the intracellular pathway of biogenesis of the protective sporozoite antigens which is essential for future production of protective antigens. Investigation of the precise mode of interaction of sporozoites with mammalian host cells and their subsequent intracellular development is undoubtedly of fundamental interest. Combined with the use of monoclonal antibodies, this in vitro system provides ideal experimental conditions for the development of a rational basis for immunological intervention targeted to interrupt parasite development and host infection.